Antigen-antibody complexes play important roles in a variety of human systemic and cutaneous diseases. This laboratory studies how immune complexes are formed, how they cause tissue damage, and how they are cleared from the circulation. We have identified and partially characterized the immunie complexes which exist in several diseases, i.e., Sjogren's syndrome, mixed cryoglobulinemia, mixed connective tissue disease, acute and chronic schistosomiasis, hepatitis and various types of cutaneous and systemic vasculitis, utilizing highly sensitive radioimmunoassays. We have developed a sensitive radioimmunoassay for the detection of IgA containing immune complexes. We have determined the antibody classes present in the immune complexes and examined the physiochemical characteristics of these complexes, as well as the reaction of these complexes with mediators of inflammation such as the complement system. We have examined the correlation between absolute levels of circulating immune complexes, the extent and severity of clinical disease, and reticuloendothelial system function. We have also examined the influence that certain genes of the major histocompatibility complex exert on immune function in vivo and in vitro in humans and demonstrated that individuals who possess the HLA-B8/DRw3 histocompatibility antigens have abnormal immunologic function both in vivo and in vitro. Since immune complexes may activate the complement system and since the complement fragments C5a and C3a are thought to be important in the pathogenesis of the inflammatory response in cutaneous and systemic diseases, we have purified C5a and studied its in vivo and in vitro reactivity Its in vivo role was assessed by the first in-depth analysis of the cutaneous reactivity of this complement fragment in man. C3a has also been purified and is currently under study.